Diabetic autonomic neuropathy is associated with an impaired vasodilator response of coronary resistance vessels to increased sympathetic stimulation, which is related to the degree of SND.

This study aimed at examining the effect of thyroid hormones on cholinergic transmission in isolated rat superior cervical ganglia (SCG). In SCG explants incubated with ³H-choline, thyroxine (T4) and 3,3’,5-triiodothyronine (T3) added to the medium before a second depolarization stimulus of 60 mM K⁺ resulted in a dose-dependent increase of S2/S1 ratio for ³H release. The concentration of hormone that produced 50% of maximal increase in K⁺-induced radioactivity release was 8 × 10^–9 M for T4 and 1.6 × 10^–8M for T3 while 3,3’,5,5’-tetraiodothyroacetic acid was almost ineffective. Preincubation of SCG with 10^–7M iopanoic acid for 30 min before S2, although not affecting by itself S2/S1 ratio, effectively prevented the increase given by T4 or T3. ³H-acetylcholine release by SCG was augmented in a high K⁺ and the effect was amplified by T4 to a similar extent as that for total ³H release. When added to the incubation medium together with 60 mM K⁺ for 30 min, T4 (10^–7M) increased significantly the activity of choline acetyltransferase (ChAT). T4 did not affect ChAT activity in SCG exposed to 4.7 mM K⁺, nor in SCG homogenates. ³H-choline uptake measured immediately after exposure of SCG to 60 mM K⁺ decreased by 25%, whereas it increased by 71% after a subsequent 30-min incubation with 4.7 mM K⁺. Addition of 10^–7M T4 prevented the changes in choline uptake observed in a high K⁺ medium. These results indicate that T4 increases SCG cholinergic transmission.

The aziridinium derivative of the compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (az-DSP4) depletes endogenous noradrenaline stores and exerts neurotoxic actions on noradrenergic neurons. These effects are persistent in the central nervous system and transient in the periphery. To determine if transmitter release plays a role in the noradrenaline depletion caused by az-DSP4, the action of the compound was studied in isolated and spontaneously beating rat atria. 1. az-DSP4 enhanced atrial beating rate when present in the incubation medium at concentrations ranging from 10(-7) M to 10(-4) M but at 10(-3) M decreased that rate below basal levels. 2. Preincubation of atria for 30 min with the noradrenaline uptake blocker desimipramine (DMI, 10(-6) M) or with the beta-blocker propranolol (10(-7) M), abolished the positive chronotropic action of az-DSP4. 3. The rate-accelerating effect of az-DSP4 could be prevented by pretreating the rats with reserpine (5 mg/kg i.p. 24 h) or enhanced by pargyline pretreatment (100 mg/kg i.p. 18 h). 4. az-DSP4 stimulated the spontaneous efflux of tritium from the isolated atria previously labeled with 3H-noradrenaline (4 X 10(-7) M), an increase that was mainly accounted for by DOPEG. 5. COMT and MAO activities in atria homogenates were inhibited by az-DSP4 in a concentration-dependent manner. However, MAO inhibition did not result in a change of the metabolic pattern as could be expected. 6. The results obtained indicate that az-DSP4 enhances the rate of spontaneous beating of isolated rat atria.(ABSTRACT TRUNCATED AT 250 WORDS)

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